Effects of age, gender, and senescence on beta-adrenergic responses of isolated F344 rat brown adipocytes in vitro.

We previously reported greater age-related attenuation of cold-induced thermoregulation and brown adipose tissue thermogenic capacity in male vs. female F344 rats. With onset of the rapid weight loss that occurs near the end of the lifespan, this age-related attenuation becomes severe. We refer to this "end-of-life" physiological state of older rats as senescence. Here, we measured oxygen consumption of isolated brown adipocytes and found no age (6 vs. 12 vs. 26 mo) or gender effects on maximal norepinephrine (NE)- or CL-316,243 (beta 3-adrenergic agonist)-induced responses. In contrast, brown adipocytes from 22- to 26-mo-old senescent rats (males and females) consumed 51-60% less oxygen during maximal stimulation with NE and CL-316,243 than did cells from 26-mo-old presenescent rats. This attenuation was associated with lower (65-72%) uncoupling protein 1 concentrations but no alterations in NE-induced cAMP levels or lipolysis. Our data indicate that senescence, but not chronological age, significantly impacts NE-/beta 3-mediated thermogenesis of isolated brown adipocytes and that this effect involves altered mitochondrial rather than altered membrane or cytosol events.